Dose-dense therapy improves survival in aggressive non-Hodgkin’s lymphoma

This study aimed to determine whether dose-dense therapy improves 3-year survival over the standard therapy for untreated aggressive lymphoma. One hundred and fifteen patients with untreated aggressive lymphoma were stratified by center, age, and international prognostic index and randomized to one of two treatment arms. One hundred and three were eligible. The experimental dose-dense arm consisted of weekly therapy with cyclophosphamide, epirubicine, vincristine, prednisolone, ifosfamide, etoposide, methotrexate, dexamethasone, and filgrastim (CEOP/IMVP-Dexa). The standard arm consisted of three-weekly cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP). The primary endpoint was overall survival after 3 years. Overall survival at 3 years was 0.766 (95% CI 0.6247, 0.8598) in the dose-dense arm and 0.462 (95% CI 0.3200, 0.5925) in the CHOP arm. Overall 5-year survival was 0.746 (95% CI 0.603, 0.843) in the dose dense and 0.406 (95% CI 0.265, 0.543) in the CHOP arm (P = 0.0062). Grade 3 and 4 infections occurred four times more frequently in the dose-dense arm. However, two patients died from toxicity in the dose-dense arm and three in the CHOP arm. Dose-dense therapy with CEOP/IMVP-Dexa is feasible and resulted in an absolute increase of 34% in the survival probability compared to CHOP in untreated patients with aggressive lymphoma.